This is a new application for a Career Transition Grant in Health Disparities (K22), which includes a 2-year intramural phase of research training in health disparities at the National Institutes of Health followed, by a 3-year extramural phase of additional mentoring and training and execution of the research plan described in this proposal. The goal of this award is to develop the candidate's expertise in gene-environment research methodology for psychiatric disorders, and to facilitate transition of the candidate into an independent research career in health disparities. The World Health Organization has projected that Major Depression will be the 2nd largest cause of disability and morbidity by the year 2020. Although epidemiological studies have documented lower rates of MDD among African-Americans than whites, blacks who suffer from the disorder evidence greater impairment and chronicity than Whites. While some research has suggested a possible protective effect against MDD caused by a higher frequency of the serotonin transporter 5-HTTLPR gene variant among Blacks, this has not been empirically supported due lack of data demonstrating an association to the MDD and related phenotypes in this population. Currently, the genetic and environmental risk factors for MDD in Blacks are poorly understood, and there have been no formal family-based studies of MDD in African-Americans. Family studies are particularly valuable because they can provide important clues about both environmental and possible genetic contributing factors to a particular illness or condition. During the extramural phase of this award, the candidate will execute a research plan, the specific aims of which are to (1) successfully recruit from the New York City area, a sample of 120 black probands with Major Depressive Disorder (MDD) and 120 non-MDD controls matched by age and sex, with up to 2 first degree relatives per proband, (2) determine the strength of the association between proband status and rates of MDD among first-degree relatives, and (3) collect DNA through extraction from saliva samples, which will be . Psychiatric history from probands and relatives will be obtained from structured diagnostic interviews and family history interviews, accompanied by questionnaires on early environmental life events, traumatic life events, and personality traits. The findings from specific aim (2) are expected to form the basis of an R01 grant to analyze the DNA collected for a gene- environment association study of MDD in African-Americans. The candidate will integrate the proposed research activities with a comprehensive mentoring and training plan, which covers family-based genetic research design and methodology (with mentor Ruth Ottman, Ph.D., and Consultant Myrna Weissman, Ph.D.), family and genetic statistics (with consultants Priya Wickramaratne, Ph.D., and Sue Hodge, Ph.D.,) and cultural and psycho-social influences on the epidemiology of Major Depressive Disorder in African-Americans (with consultant James Jackson, Ph.D). PUBLIC HEALTH RELEVANCE: Major Depressive Disorder, a disease from which African-Americans experience more impairment, morbidity and chronicity than Whites, is expected to be the second largest cause of morbidity and mortality by the year 2020. African-Americans are underrepresented in formal family studies, which have shown this disorder to highly familial, with genetic and environmental contributions. This family-based genetic study of Major Depression will be an important step in addressing a critical gap in the current knowledge etiological factors of Major Depressive Disorder in African-Americans.